Fernández-Nogueira et al. discovered that tumor fibroblasts could induce tumor cell resistance to trastuzumab in HER2-positive breast cancers, and they found that HER2-positive TAFs (tumor-associated fibroblasts) secreted FGF5 (fibroblast growth factor 5), which connects to fibroblast growth factor receptor 2 (FGFR2) to transactivate HER2 by phosphorylating the c-Src proto-oncogene. This evidence concerns the gene ERBB2 and breast cancer.